Biomedical subjects
Publications and source records attributed to Kim N Dietrich.
This pilot study investigated adolescents with well-documented childhood lead burdens to determine the relationship between lead and unintentional injury. Adolescents completed a self-administered injury questionnaire. Results demonstrated that elevated childhood blood lead concentrations were significantly related to injury variables. Further study is necessary to understand adolescent health and safety implications.
This prospective study investigated the impact of early exposure to lead on the maturation of children's postural balance. The effect of lead exposure on age-associated maturation of postural balance was investigated on 91 children from the Cincinnati Lead Study (CLS) with a 5-year geometric mean lead concentration in blood of 11.66 microg/dL (range 3.89-28.33 microg/dL) by re-assessing their postural balance approximately every 20 months starting at mean age of 6.6 years through mean age of 12.1 years. The results presented in this paper provide evidence that low to moderate lead exposure in early childhood has a measurable and statistically significant impact on the maturation of postural balance. In comparison to less exposed children, of those in the higher lead group showed an impaired postural balance response. The results from this study suggest that children with early childhood lead exposure may need additional time to approach (or "catch up" with) their maturational postural balance status. As these subjects are now adults in their early to mid-twenties, poor postural balance may impact their daily living tasks and pose a higher risk of potential injuries at home and work.
OBJECTIVES: The purpose of this work was to assess the long-term impact of childhood lead exposure on the neurosubstrate of language function and brain organization. METHODS: Young adults from the Cincinnati Lead Study were recruited to undergo functional magnetic resonance image scanning while performing a verb generation task. These subjects have been followed from birth through early childhood with extensive documentation of lead exposure, neuropsychology, and behavior. Forty-two subjects provided useful imaging data. The locale, strength, and the correlation between brain language activation and childhood blood lead concentration were studied. RESULTS: After adjusting for potential confounders, the activation in left frontal cortex, adjacent to Broca's area, and left middle temporal gyrus, including Wernicke's area, were found to be significantly associated with diminished activation in subjects with higher mean childhood blood lead levels, whereas the compensatory activation in the right hemisphere homolog of Wernicke's area was enhanced in subjects with higher blood lead levels. CONCLUSION: This study indicates that childhood lead exposure has a significant and persistent impact on brain reorganization associated with language function.
Increases in peak blood lead concentrations, which occur at 18-30 months of age in the United States, are thought to result in lower IQ scores at 4-6 years of age, when IQ becomes stable and measurable. Data from a prospective study conducted in Boston suggested that blood lead concentrations at 2 years of age were more predictive of cognitive deficits in older children than were later blood lead concentrations or blood lead concentrations measured concurrently with IQ. Therefore, cross-sectional associations between blood lead and IQ in school-age children have been widely interpreted as the residual effects of higher blood lead concentrations at an earlier age or the tendency of less intelligent children to ingest more leaded dust or paint chips, rather than as a causal relationship in older children. Here we analyze data from a clinical trial in which children were treated for elevated blood lead concentrations (20-44 microg/dL) at about 2 years of age and followed until 7 years of age with serial IQ tests and measurements of blood lead. We found that cross-sectional associations increased in strength as the children became older, whereas the relation between baseline blood lead and IQ attenuated. Peak blood lead level thus does not fully account for the observed association in older children between their lower blood lead concentrations and IQ. The effect of concurrent blood level on IQ may therefore be greater than currently believed.
Principles and practices of pediatric neurotoxicology are reviewed here with the purpose of guiding the design and execution of the planned National Children's Study. The developing human central nervous system is the target organ most vulnerable to environmental chemicals. An investigation of the effects of environmental exposures on child development is a complex endeavor that requires consideration of numerous critical factors pertinent to a study's concept, design, and execution. These include the timing of neurodevelopmental assessment, matters of biologic plausibility, site, child and population factors, data quality assurance and control, the selection of appropriate domains and measures of neurobehavior, and data safety and monitoring. Here we summarize instruments for the assessment of the neonate, infant, and child that are being employed in the Centers for Children's Environmental Health and Disease Prevention Research, sponsored by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency, discuss neural and neurobiologic measures of development, and consider the promises of gene-environment studies. The vulnerability of the human central nervous system to environmental chemicals has been well established, but the contribution these exposures may make to problems such as attention deficit disorder, conduct problems, pervasive developmental disorder, or autism spectrum disorder remain uncertain. Large-scale studies such as the National Children's Study may provide some important clues. The human neurodevelopmental phenotype will be most clearly represented in models that include environmental chemical exposures, the social milieu, and complex human genetic characteristics that we are just beginning to understand.
Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 microg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 microg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5-10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 microg/dL and declined to 9.4 microg/dL by 5-7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 microg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 microg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a log-linear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2-9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 microg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 microg/dL, 10 to 20 microg/dL, and 20 to 30 microg/dL were 3.9 (95% CI, 2.4-5.3), 1.9 (95% CI, 1.2-2.6), and 1.1 (95% CI, 0.7-1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 microg/dL was significantly greater than that observed for those with a maximal blood lead level > or = 7.5 microg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 microg/dL is associated with intellectual deficits.
One hundred and ninety-five participants in the Cincinnati Lead Study were neuropsychologically evaluated in mid-adolescence. The neuropsychological measures yielded five factors labeled Memory, Learning/IQ, Attention, Visuoconstruction, and Fine-Motor. Prenatal, Average Childhood, and 78 month blood lead (PbB) levels were used in a series of multiple regression analyses. Following rigorous covariate pretesting and adjustment, a significant main effect of 78 month PbB on the Fine-Motor factor was found (p <.004). Significant interactions were also found between gender and lead exposure parameters for both Attention and Visuoconstruction indicating heightened risk in males. Finally, a trend toward significance was found for the PbB x SES interaction for Learning/IQ, consistent with previous evidence of increased educational and cognitive vulnerability for youth from more disadvantaged backgrounds. These results provide new evidence from the longest continuing prospective study of the remote effects of early lead exposure. They indicate the presence of selective neuropsychological effects in this population, and also that males and females are not uniformly affected. These results also underscore the complexity of models of neurobehavioral development, and the modest predictive power of any single determinant.
Although there is empirical support for the link between executive functioning (EF) and visual memory among adults, there has been less exploration of this link among children, especially adolescents. We examined the relation between several EF measures and performance on the Rey-Osterrieth Complex Figure (RCF) in a sample of 160 community adolescents. Each was administered the Wisconsin Card Sorting Test (WCST), Conners Continuous Performance Test (CPT), and the RCF, scored using Bernstein and Waber's (1996) Developmental Scoring System (DSS). Ability to organize the RCF related to memory encoding/retrieval, but not to long-term storage. Indexes derived from the WCST and CPT failed to correlate with any RCF index, raising questions about the relation between DSS scores and EF. Even so, data supported the convergent validity of the DSS system as a reflection of visual-constructional ability and provided evidence of the importance of organizational strategies to visual memory among adolescents.
OBJECTIVE: Some children in the United States continue to be exposed to levels of lead that increase their risk for lowered intellectual functioning and behavior problems. It is unclear whether chelation therapy can prevent or reverse the neurodevelopmental sequelae of lead toxicity. The objective of this study was to determine whether chelation therapy with succimer (dimercaptosuccinic acid) in children with referral blood lead levels between 20 and 44 microg/dL (0.96-2.12 micromol/L) at 12 to 33 months of age has neurodevelopmental benefits at age 7 years. METHODS: The Treatment of Lead-Exposed Children (TLC) study is a randomized, double-blind, placebo-controlled trial that was conducted between September 1994 and June 2003 in Philadelphia, PA; Newark, NJ; Cincinnati, OH; and Baltimore, MD. Of 1854 referred children who were between the ages of 12 to 33 months and screened for eligibility, 780 were randomized to the active drug and placebo groups stratified by clinical center, body surface area, blood lead level, and language spoken at home. At 7 years of age, 647 subjects remained in the study. Participants were randomly assigned to receive oral succimer or placebo. Up to 3 26-day courses of succimer or placebo therapy were administered depending on response to treatment in those who were given active drug. Eighty-nine percent had finished treatment by 6 months, with all children finishing by 13 months after randomization. All participants received residential lead hazard control measures before treatment. TLC subjects also received a daily multivitamin supplement before and after treatment(s) with succimer or placebo. Scores on standardized neuropsychological measures that tap cognition, behavior, learning and memory, attention, and neuromotor skills were measured. RESULTS: Chelation therapy with succimer lowered average blood lead levels for approximately 6 months but resulted in no benefit in cognitive, behavioral, and neuromotor endpoints. CONCLUSION: These new follow-up data confirm our previous finding that the TLC regimen of chelation therapy is not associated with neurodevelopmental benefits in children with blood lead levels between 20 and 44 microg/dL (0.96-2.17 micromol/L). These results emphasize the importance of taking environmental measures to prevent exposure to lead. Chelation therapy with succimer cannot be recommended for children with blood lead levels between 20 and 44 microg/dL (0.96-2.12 micromol/L).
Maintaining upright posture is a complex process involving multiple afferent systems. The aim of this study was to measure the postural stability of children with Autism Spectrum Disorder (ASD) compared with children with typical neurodevelopment and to measure the relative contributions of the visual, somatosensory, and vestibular afferent systems in each group. Eight boys with ASD and eight age-, race-, and gender-matched controls participated in this study using force platform technology with customized software to measure postural sway under conditions designed to eliminate or modify visual and somatosensory input. Children with ASD had significantly larger sway areas under all test conditions in which afferent input was modified. These results are consistent with a deficit in the integration of visual, vestibular, and somatosensory input to maintain postural orientation.
The effect of lead exposure on cognitive growth patterns was assessed in a longitudinal study of 196 children. Performances on tests of verbal comprehension and perceptual organization (Vocabulary & Block Design, Wechsler Intelligence Scales for Children) were measured at ages 6.5, 11 and 15 years. Growth curve analyses revealed that the quadratic model best described the relationship between test scores and age. Children with higher lead levels, as measured at age 15 years, demonstrated lower verbal comprehension scores over time and greater decline in their rate of Vocabulary development at age 15 years, as compared to children with lower lead levels. Lead exposure was not significantly associated with growth in perceptual organization test scores. Socioeconomic status and maternal intelligence were statistically significantly associated with growth patterns for both test scores, independent of the effects of lead. The findings suggest that lead negatively impacts the developmental progression of specific cognitive skills from childhood through adolescence.
OBJECTIVE: Exposure to lead at levels encountered by urban children impairs cognitive development. An observational study suggested improvement in IQ when blood lead level fell, but the only randomized trial of chelation showed no benefit in IQ. METHODS: We did a new analysis of the data from the clinical trial using change in blood lead level as the independent variable. The 741 children began with blood lead levels between 20 and 44 microg/dL, and were 13 to 33 months old at randomization to chelation or placebo. Blood lead levels were measured repeatedly, and cognitive tests were given at baseline, 6 months, and 36 months follow-up. RESULTS: By 6 months after randomization, blood lead levels had fallen by similar amounts in both chelated and placebo children, despite the immediate drops in the chelated group; there was no association between change in blood lead level and change in cognitive test score. Blood lead levels continued to fall. At 36 months follow-up, in the placebo group only, cognitive test scores had increased 4.0 points per 10 microg/dL fall in blood lead level from baseline to 36 months follow-up and 5.1 points from 6 to 36 months. CONCLUSIONS: The improvement in scores in the placebo group only implies that factors other than declining blood lead levels per se are responsible for cognitive improvement; it is possible but less likely that succimer, the active drug, impairs cognition.
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OBJECTIVE: In children, lead can cause serious permanent damage as a neurotoxicant. The objectives of the study were to evaluate potential exposure to lead-based paint in family housing units at a typical U.S. military installation and determine blood lead (PbB) levels in children ages 6 years or younger residing in these housing units. METHODS: The authors conducted a risk assessment of 1,723 housing units and occupants at Fort Devens in Massachusetts. Data from the military dependent cohort was compared to estimates for the U.S. national population as reported from Phase 1 of the Third National Health and Nutrition Examination Survey (NHANES III). RESULTS: A total of 1992 individuals (1,009 males and 983 females) were screened for PbB, stratified into age groups, and separated into racial/ethnic categories. Four (0.3%) dust samples and 59 (11.6%) internal and 298 (77.8%) external paint chip samples contained hazardous levels of lead. The geometric mean PbB concentration for people ages 1 year and older reported by NHANES III was 2.8 micro g/dL, compared with 1.5 microg/dL for the military installation cohort (p<0.0001). PbB levels were higher for males than for females and higher for blacks than whites 6 years of age and older. Hispanics had lower PbB concentrations for all age groups except for those ages 1-2.9 years. Prevalence of PbB levels >10 microg/dL for all age groups was 1.6% in the military cohort, compared with 4.5% for the general population. For ages 1-2.9 years, no blacks or Hispanics and 0.6% of whites had PbB levels >10 micro g/dL, compared with 21.6% of blacks, 10.1% of Hispanics, and 8.5% of whites for the general population. For ages 3-5.99 years, 0.15% of blacks, 0% of Hispanics, and 0.3% of whites had PbB levels > or = 10 microg/dL, compared with 20.0% of blacks, 6.8% of Hispanics, and 3.7% of whites for the general population. CONCLUSION: Lead exposure for occupants of on-post military housing is much less than for those residing in the civilian sector.
During the past 2 decades, the proportion of US children who have blood lead concentrations of 10 microg/dL or higher declined by over 80% after the elimination of leaded gasoline and lead solder from canned foods, and a ban on leaded paint used in housing and other consumer products. Fatalities and symptomatic lead poisoning are now rare. Residential lead hazards, which are exceedingly difficult to control, are currently the major source of lead intake for children. Undue lead exposure has retreated into 2 major risk groups; impoverished children who live in older, poorly maintained rental housing and more affluent children who live in older housing undergoing renovation. Despite the dramatic decline in children's blood lead levels, lead toxicity remains epidemic among impoverished children who live in older rental housing, especially those who live in the northeastern and midwestern regions of the United States. There are increasing data linking lead exposure with other systemic effects including delinquency, dental caries, and learning problems. Moreover, there is evidence indicating that there is no discernible threshold for lead-associated cognitive deficits. Thus, it is increasingly important to shift our efforts toward the primary prevention of childhood lead exposure from residential hazards. This article reviews the epidemiology and control of childhood lead exposure, focusing especially on steps necessary to shift toward primary prevention.